Design, synthesis, and anti-breast tumor activity of novel combretastatin A-4 analogues

We reported the design, synthesis, and biological evaluation of 9 novel benzofuran analogues of CA-4 and their preliminary structure-activity relationship with inhibitory activity on microtubules and the phosphoinositide 3-kinase (PI3K). Various spectroscopic techniques like 1H NMR, 13C NMR, and HRMS were used for characterization of all synthesized analogs. Among these derivatives, most compounds inhibited the growth of breast tumor cell lines, especially one compound showed prominently inhibitory activity in MCF-7 and MDA-MB-231 cells with IC50 value as 3.88 and 5.78 & mu;mol/dm3. Furthermore, we found that the same compound reduced the PI3K expression levels, conversely elevated the & beta;-tubulin expression levels in enzyme-linked immunosorbent assay. The binding interactions between synthesized analogs and colchicine active site of tubulin protein and the PI3K & alpha; protein were confirmed through molecular docking study. These preliminary results showed that this compound has the potency for further study as a dual-target anti-tumor inhibitor.